The development of potent vaccine against Plasmodium falciparum malaria could alleviate the disastrous effects of a major public health problem. While effective malaria control programs are urgently needed, previous efforts to develop a useful vaccine have met with limited success. Our lab has used an in vivo protective immunization strategy to identify and characterize novel protective antigens of Plasmodia. Initial studies indicate that at least one of three antigens we have cloned can induce protective immunity against P. yoelti blood-stage infection. This proposal focuses on this related group of P. yoelii cDNA clones. The specific aims of may work are; 1) To complete the screening of recombinant antigens derived from the major group of three related P. yoelii cDNA clones for their ability to immunize against blood-stage P. yoelii infection. 2) To develop DNA and antibody probes based on the most protective P. yoelii antigen, to be used for the identification of the homologous antigen gene of P. falciparum. 3) To construct and screen a P. falciparum cDNA expression library in order to clone this novel P. falciparum vaccine candidate antigen. 4). To characterize the P. falciparum antigen sequence by DNAS sequence, Southern blot and northern blot analyses. We believe that with this approach we can identify and characterize a novel P. falciparum antigen to be used in the development of a potent vaccine against humans malaria.